April 13, 2007
Macaques May Have Plenty to Say About Us
By David Brown

As primates were climbing the evolutionary tree 25 million years ago -- and long before ancestral human beings climbed down from real trees -- strange things were happening in their genomes.

Errors that creep into genes, and are usually quickly expunged, suddenly became more tolerable. Pieces of DNA left over from ancient viral infections sometimes just got up and moved. New hingelike structures on chromosomes, called centromeres, appeared out of nowhere. The chemical dialect that cells use to talk was also changing, and something weird was happening to primate hair.

Those are among the insights from the rhesus macaque genome, an early analysis of which is in five papers appearing today in the journal Science.

Also known as the rhesus monkey, it is the third primate whose genome has been copied. The others are humans and chimpanzees.

The work, done over two years by more than 170 scientists, is expected to provide unusual insight into human evolution. It provides the genetic portrait of a species between our closest relative, the chimpanzee, and far more distantly related ones, such as dogs and mice, whose genomes have also been copied.

"It gives us a key intermediate position; it lets us reach back a little farther into our evolutionary history," said Adam Siepel, a computational biologist at Cornell University in Ithaca, N.Y., and a member of the consortium.

A genome includes a species's DNA, which exists in long chainlike structures called chromosomes. Some of the DNA is in the form of genes, which carry the instructions cells use to make proteins. Some is non-coding DNA that regulates the genes. Some is structural filler. A lot is "junk" DNA, whose purpose, if any, is still largely unknown.

The biologists did not find any "smoking guns" of evolution when they compared the macaque genome with the human and chimpanzee genomes. "The explanation of the difference between species is complicated. It is going to be a story with a lot of small parts," Siepel said.

They did find that in the 25 million years since the three species had a common ancestor, natural selection has preserved more mutations in the chimp and human genomes than in the macaque's.

That suggests that chimps and humans were under evolutionary pressure to change -- perhaps because of altered environments or new competition -- while macaques (like dogs and mice) were in more stable circumstances and thus less receptive to mutations.

About 180 genes appear to have undergone especially large changes in chimps and humans. They include genes for immune defense and cell-to-cell communication and attachment. Curiously, two are involved in hair-shaft formation. The researchers speculated that climate change or mate selection might have driven their evolution.

The scientists also found that 14 new centromeres arose in the three primate species in the past 25 million years. Each chromosome has a centromere midway down its shaft that plays a crucial role in cell division. That number was "unexpected," they wrote, and suggests that the replacement of old centromeres with new ones is key in evolution.

They also found more than a half-million fragments of ancient retroviruses in the macaque junk DNA. Retroviruses can stitch themselves into a cell's DNA; the best-known one is HIV (human immunodeficiency virus), which causes AIDS.

"It is pretty clear that macaques appear to have been historically more susceptible to retroviral infection than the human lineage," said Mark A. Batzer of Louisiana State University at Baton Rouge, one of the project leaders.

Curiously, the two big populations of rhesus macaques -- one native to India and the other to China -- respond differently to simian immunodeficiency virus, the monkey version of HIV. The Chinese monkeys get sick and die much more slowly than the Indian ones. AIDS researchers now hope that by pinpointing small differences in the two genomes they will be able to understand why.

Macaques are also widely used in other fields of medical research, including the testing of new drugs. Understanding their genome may allow researchers to use them more wisely, said Richard A. Gibbs of Houston's Baylor College of Medicine, who headed the project.